Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia
Authors: Jane A. O’Halloran, Emily R. Ko, Kevin J. Anstrom, Eyal Kedar, Matthew W. McCarthy, Reynold A. Panettieri, Martin Maillo, Patricia Segura Nunez, Anne M. Lachiewicz, Cynthia Gonzalez, P. Brian Smith, Sabina Mendivil-Tuchia de Tai, Akram Khan, Alfredo J. Mena Lora, Matthias Salathe, Gerardo Capo, Daniel Rodríguez Gonzalez, Thomas F. Patterson, Christopher Palma, Horacio Ariza, Maria Patelli Lima, John Blamoun, Esteban C. Nannini, Eduardo Sprinz, Analia Mykietiuk, Radica Alicic, Adriana M. Rauseo, Cameron R. Wolfe, Britta Witting, Jennifer P. Wang, Luis Parra-Rodriguez, Tatyana Der, Kate Willsey, Jun Wen, Adam Silverstein, Sean M. O’Brien, Hussein R. Al-Khalidi, Michael A. Maldonado, Richard Melsheimer, William G. Ferguson, Steven E. McNulty, Pearl Zakroysky, Susan Halabi, Daniel K. Benjamin, Sandra Butler, Jane C. Atkinson, Stacey J. Adam, Soju Chang, Lisa LaVange, Michael Proschan, Samuel A. Bozzette, William G. Powderly, Mahendra Patel, Arun Sanyal, Jason Green, Huimin Wu, Benjamin Linas, Philip Grant, Vivek Iyer, Otto Yang, Bindu Balani, Sam Parnia, Ryan Dare, Caryn G. Morse, Estelle S. Harris, Glenn Wortmann, Nicholas Hill, Shama Patel, Julia Garcia-Diaz, Suman Thapamager, Megan Devine, Christine M. Bojanowski, Barry Meisenberg, Gailen Marshall, Dima Dandachi, Arick Sabin, Anthony Breemo, Suman Sinha, Christopher Goss, Rebecca Reece, Arlette Aouad, Seth Glassman, Peter Morris, Bela Patel, Fatimah Bello, Juliana Cardozo Fernandes, Oscar Carbajal, Lorena Ravera, Mozar Castro, Miguel Villegas-Chiroque, Fernando Oscar Riera, Adrian Camacho, Claudio Stadnik, Jorge Gave, Rodrigo Biondi, Ronal Gamarra Velarde, Jose Cerbino Neto, Juan Ditondo, Marcelo H. Losso, Mariano Dolz, Alexandra O’Sullivan, Brian Gavin, Maria Beumont-Mauviel, Huyen Ca, Rose Beci, Daniel Molina, Sandhya Rao, Thomas Stock, William Erhardt, Sarah Read, Jessica Springer, Rachel Presti, Ryley Thompson, Kimberly Gray, Cathy Henry, Alem Haile, Michael Klebert, Lisa Kessels, Kathryn Vehe, Kristopher Bakos, Teresa Spitz, Sara Hubert, Raghd Alyatim, Brittany Schneider, Chapelle Ayres, Andrej Spec, Laura Blair, Anita Afghanzada, Natalie Schodl, Lana Wahid, John J. Engemann, Gloria Pinero, Beth McLendon-Arvik, Lynn Whitt, Jenny Shroba, Elizabeth Salsgiver, Candace Alleyne, Anna Gwak, Nicholas Pickell, Jack Spagnoletti, Samson Goh, Katharine Robb, Michael Cenname, Catherine Small, Markus Plate, Rodrigo Burgos, Brenna Lindsey, Fischer Herald, Stephanie Echeverria, Dorendra Lewis, Mahesh Patel, Charles D. Bengtson, Andreas Schmid, Kimberly Lovell, Carly Lovelett, Daniel Soule, Daniel Jaremczuk, Jennie Flanagan, Cameron Murray, Kylie Sands, Kyle Flint, Sara Mohaddes, Caryn Harrington, Kylie Broughal, David Sogoian, Karen Cox, Heta Javeri, Philip O. Ponce, Danielle O. Dixon, Jason E. Bowling, Jan E. Patterson, Barbara S. Taylor, Ruth C. Serrano, Kaylin Sallee, Robin Tragus, Gabriel Catano, Irma Scholler, Rose Ann Barajas, Armando Garcia, Bridgette Soileau, Patricia Heard, Manuel Camilo Endo Carvajal, Rukevwe Ehwarieme, Divya Chandramohan, Alejandro Cabo, Abdelhameed Nawwar, Caroline M. Quill, Nayeem Choudhury, Ashley Arrington, Isaiah Holyfield, Abby Smith, Glenda Brown, Kyle Varner, Joni Baxter, Tracy Roundy, Mary Co, Mireya Wessolossky, Juan Perez-Velazquez, Jennifer Holter-Chakrabarty, Brittany Karfonta, Juvaria Anjum, Jai Marathe, Myriam Castagne, Daniel Mompoint, Ryan Schroeder, Mallika Rao, Johnathan Nguyen, Jake Plewa, Sue Donlinger, Marylynn Breslin, Susan Dodson, Mitch Jenkins, John Williamson, Elizabeth A. Middleton, Mai Tavadze, Romai Sebhatu, Jessica Pierobon, Nate Miller, John Lee, Pratik Doshi, Andrew Dentino, Jessica Martin, Erik Hinojosa, Pablo Torres, Ricardo Sanchez, Gladys Murga, Silvana de la Gala, Jhon Chaiña, Jorge Ramos, Jenny Malca, Kathia Castillo, Johana Calderon Galvez, Maria Lyda Icochea Perez, Claudia Carolina Becerra Nunez, Sandra Betteta Riondato, Sandra Delgado Málaga, Cecilia Barreda Sánchez, Sylvia Sánchez Morales, Myriam Yaringano Palacios, Dora Galarza Cuba, Ivan Hermenegildo, Mayra Falla Benites, Stefania Neyra, Josefina Hernández, Victoria García, Katherine Palacios, Miluska Matos, Fiorella Zuloeta, Fiorella del Carpio, Gloria Chacaltana, Carmen de la Cruz, Felipe Ceriolli Breda, Mauricio Mello Roux Leite, Tobias Milbradt, Luz Rodeles, Nadia Benzaquen, Sebastian Pezzini, Lucila Alberdi, Priscila Serravalle, Giulia Russo, Franco Ferini, Maria Eugenia Guala, Alejandro Crespo, Agostina Benitez, Maria Elena Cristaldi, Paula Di Renzo, Corina Gramagalia, Antonela Tessini, Joana Evelin Alonso, Carmen Pic, Georgina Ceraldi, Azucena Mondino, Iliana Higareda Almaraz, Víctor Hugo Madrigal Robles, María Fernanda Rosas Ismerio, Maria Fernanda Rodarte Rodriguez, Norma Esther Olmos Meza, Norma Esther de la Cruz Barba, Ana Maria Alba Ponce, Juan Manuel Calderon, Eduardo Borsetta, Noemí Sandoval, Daniela Vazquez, Malena Mansilla, Marta Molina, Yamila Jara, Laura De Bona, Maria Eduarda Claus, Arthur Pille, Matías Lahitte, Mariángeles Fenés, Cecilia Bianchi, María Emilia Miserere, Maria Fernanda Alzogaray, Halbert Christian Sanchez Carrillo, Aldana Mano, Myrna Zuain, Javier J. Toibaro, Valeria Pachioli, Sebastián Chaio, Natalia Malamud, David B. Bharucha, Patrick Dorr, Jonathan Sadeh, Sheila Kelly, Marita Stevens, Huyen Cao, Adam DeZure, Kavita Juneja, Mazin Abdelghany, Theresa Jasion, Rachel Olson, Megan Roebuck, Jacqueline Huvane, Christopher J. Lindsell, Jeff Leimberger, Eric Yow, Zhen Huang, Hwasoon Kim, Carla Anderson, Carrie Elliott, Merri Swartz, Jyotsna Garg, Neta Nelson, Divya Kalaria, Ketty Philogene, Tim Schulz, Averie Kuek, Fatou Bah, Jarrard Mitchell, Elizabeth Polo, Michelle Wong, Sharon Baldan, Sandra Mendez, Bradford Stevens, Marcela Toledo, Talita Abba, Emma Herrejon, Cristina Gomez, Georgeta Mardari, Neeraja Putta, Robin Mason, Holli Hamilton, Derek Eisnor, Anna O’Rourke, Aditi Patel, Betty Brody, Anna Chiang, Brian Lind, Lilli M. Portilla, Ami D. Gadhia, Sury Vepa, Emily Carlson Marti, Bobbi Gardner, Joni Rutter, Clare Schmitt, Michael Kurilla
Journal: JAMA (2023)

Importance Immune dysregulation contributes to poorer outcomes in COVID-19. Objective To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. Design, Setting, and Participants Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021. Interventions Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day). Main Outcomes and Measures The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale. Results Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies. Conclusions and Relevance Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. Trial Registration ClinicalTrials.gov Identifier: NCT04593940